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Updated: Nov 17, 2025
Application of Laser Microdissection to Uncover Regional Transcriptomics in Human Kidney Tissue
Published on: June 9, 2020
Whole-Exome Sequencing Reveals New Potential Mutations Genes for Primary Mucosa-Associated Lymphoid Tissue Lymphoma
Shuang Wen1, Tianqing Liu1, Hongshuo Zhang2
1Department of Pathology, Dalian Friendship Hospital, Dalian, China.
Abstract:
Low-grade B cell lymphomas of mucosa-associated lymphoid tissue (MALT) lymphomas involving the kidney were extremely rare, genetic alteration or molecular features was not yet explored, which may lead to limited choices for postoperative adjuvant or targeted. Whole-exome sequencing based tumor mutation profiling was performed on the tumor sample from a 77-year-old female presenting with discomfort at the waist was pathologically diagnosed as MALT lymphomas in the right kidney. We identified 101 somatic SNVs, and the majority of the identified SNVs were located in CDS and intronic regions. A total of 190 gain counts of CNVs with a total size of 488,744,073 was also investigated. After filtering with the CGC database, seven predisposing genes (ARID4A, COL2A1, FANCL, ABL2, HSP90AB1, FANCA, and DIS3) were found in renal MALT specimen. Furthermore, we compared somatic variation with known driver genes and validated three mutational driver genes including ACSL3, PHOX2B, and ADCY1. Sanger sequencing of germline DNA revealed the presence of a mutant base T of PHOX2B and a mutant base C of ADCY1 in the sequence, which were discovered for the first time in MALT lymphomas involving the kidney. Moreover, immunohistochemical analysis revealed that tumor cells were positive for CD20, CD79a, PAX5, CD21, and CD23, and expression of CD3, CD5, and CD8 were observed in reactive T lymphocytes surrounding tumor cells. These findings illustrated that concurrent aberrant PHOX2B and ADCY1 signaling may be a catastrophic event resulting in disease progression and inhibition of the putative driver mutations may be alternative adjuvant therapy for MALT lymphoma in the kidney which warrants further clinical investigation.
Insights
This study reveals novel genetic alterations in rare kidney MALT lymphomas, identifying PHOX2B and ADCY1 as key drivers. Targeting these mutations may offer new therapeutic avenues for this uncommon cancer.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Low-grade B cell lymphomas of mucosa-associated lymphoid tissue (MALT) lymphomas involving the kidney are exceptionally rare.
- Limited understanding of genetic alterations and molecular features hinders effective treatment strategies for renal MALT lymphomas.
Purpose of the Study:
- To explore the genetic landscape and molecular features of kidney MALT lymphomas.
- To identify potential therapeutic targets for this rare malignancy.
Main Methods:
- Whole-exome sequencing (WES) was employed for tumor mutation profiling.
- Copy number variation (CNV) analysis and filtering against the Cancer Gene Census (CGC) database were performed.
- Somatic variation analysis was compared with known driver genes, and key mutations were validated using Sanger sequencing.
- Immunohistochemical analysis characterized tumor cell markers and surrounding immune cells.
Main Results:
- 101 somatic single nucleotide variants (SNVs) and 190 copy number gains were identified.
- Seven predisposing genes and three validated mutational driver genes (ACSL3, PHOX2B, ADCY1) were found.
- Novel mutations in PHOX2B and ADCY1 were discovered in the renal MALT lymphoma specimen.
- Immunohistochemistry confirmed B-cell markers on tumor cells and T-cell infiltration.
Conclusions:
- Concurrent aberrant PHOX2B and ADCY1 signaling may drive disease progression in kidney MALT lymphomas.
- Inhibition of these driver mutations could represent a novel adjuvant therapy approach.
- Further clinical investigation is warranted to explore targeted therapies for renal MALT lymphoma.
